Pretest self-assessment question (answer at the end of the case)
Which of the following evidence-based antidepressant augmentations likely has the least side-effect burden?
A. SAMe
B. Lithium carbonate
C. Aripiprazole
D. Thyroid hormone
Patient evaluation on intake
52-year-old man cannot sleep
He has been “in a funk” for about a year after he had difficulty at his work site
Psychiatric history
The patient has been emotionally well his whole life
About a year ago, developed vision problems due to diabetes, which interfered with his ability to work safely at his job site as an assembly line worker
He was placed on lighter duty and then ultimately laid off due to bad economic times
At the time of his transition to light duty, he began experiencing psychiatric symptoms as follows
– Insomnia
– Dysphoria and irritability
– Increasing anhedonia
– Poor concentration
– Poor appetite
– Feelings of worthlessness and hopelessness
– Fatigue
– He denied suicidal thoughts, or psychotic, manic, anxiety, and substance misuse symptoms
Social and personal history
Married with five adult children
Takes care of his grandchildren often and might be considered a primary caregiver
Has tenth grade education
Gainfully employed as an assembly line worker for many years until recently
Most of his friends, support, and identity as an autoworker were disrupted when he was forced to leave work
He does not abuse substances, nicotine, or caffeine
Medical history
Family history
One son has bipolar disorder and substance abuse problems
Mother suffered from MDD
AUD is present in multiple family members at each generation
Psychotherapy history
Started supportive psychotherapy several weeks ago
Attendance is good
Feels better after sessions but this is short lived
Patient evaluation on initial visit
Current medications
Question
Greasy hands? Is that a real side effect?
No, it is hypochondriacal, hysterical, or a nocebo side effect
No, it is not listed in the regulatory package insert for sertraline
Yes, a web search reveals that two to three other patients have posted similar experiences
Yes, it is likely a paresthesia, and these occur in 1% of patients taking sertraline
Yes, it is a side effect because the patient says it is, and it bothers him
Attending physician’s mental notes: initial evaluation
This patient has an index episode of MDD that is moderate in severity
This was likely initiated due to an interpersonal loss and social stressor when his working career ended beyond his control
He may be starting to respond to his inaugural SSRI at this time, but has a strange side effect where his hands feel greasy, or as if they were immersed in liquid
He does not appear to have any comorbid psychiatric conditions
He has some chronic medical problems but they appear stable and well controlled
He is not felt to be suicidal
Question
Which of the following would be your next step?
Do nothing as his SSRI is starting to become effective after three weeks of use
His side effects are strange but minor; convince him to tolerate his medication longer
Increase the SSRI for better effect
Change to an alternate SSRI in the hope of continuing this early efficacy but without the paresthesia
Change classes to a different family of antidepressant
Add an anti-paresthesia medication such as gabapentin (Neurontin)
Refer for specific IPT, which is well studied for depression when caused by interpersonal role change such as a loss of work
Attending physician’s mental notes: initial evaluation (continued)
The patient is somewhat better after three weeks of SSRI treatment, but this equates to 20% better at most, as only two MDD symptoms are minimally better
If patient can tolerate his side effect a bit more and given this initial small response, it may make sense to increase his current SSRI, sertraline (Zoloft) further
Further investigation
Is there anything else you would especially like to know about this patient?
Could there be any other cause to the strange sensations in his hands?
– Physical examination reveals no clear skin changes or deformities
– He has full range of motion, no arthritic changes
– He has no history of cervical injury or pain
– None of the medications are known to cause this kind of side effect
– There is no evidence of carpal tunnel or other entrapment syndrome
– Discussions with his PCP confirms these findings
– He has leg pain and neuropathy from his diabetes, it is possible that these hand pressure sensations are the start of diabetic neuropathy in his upper extremities that presented coincidentally with the start of his SSRI
Case outcome: first interim follow-up visits through three months
Agrees now to increase the SSRI sertraline (Zoloft) to 100 mg/d and to tolerate the side effect of greasy hands as it is explained that it may be a rare side effect or part of his DM2
Later feels better but qualifies this as being less ruminative, less tense, and sleeping better, but still often feels amotivated and dysphoric
The SSRI dose is raised to 150 mg/d and he returns with moderate, sustained improvement in these symptoms and he feels his appetite is better
Question
Do the SSRIs have a dose–response curve where greater doses treat a greater number of symptoms?
No, according to regulatory information, there is no additional benefit between low, moderate, and high doses of SSRI when used to treat MDD
No, studies suggest that low doses of SSRI successfully inhibit the SERT, indicating that further inhibition is likely not needed for greater antidepressant response
Yes, in clinical practice, many clinicians claim that higher doses usually aid in more symptom reduction
Yes, textbooks and a recret meta-analysis suggest higher dosing on an individual basis to deliver the highest effectiveness
Possibly, as regulatory trials often contain 300–400 subjects and are statistically designed to show that all doses are superior to placebo but not necessarily to each other
– They are not designed with enough subjects, i.e., 1500 or enough statistical power to show discrete differences between low, middle, and higher doses
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